Abstract West Virginia (WV) has the highest drug overdose fatality and hepatitis B rates in the U.S.A., especially in the rural southern coalfield counties. While no known HIV outbreaks have yet occurred in these areas, they are a ?ticking time bomb?, especially as the current ability to detect and mitigate an outbreak is poor. WV has been devastated economically by the collapse of the coal industry. Economic devastation, coupled with the ready availability of prescription opioids, led to an explosive epidemic that has transitioned from oral pills to heroin injection. The threat of an HIV outbreak here is among the highest in the U.S.A. per CDC?s analysis of the 2014- 2015 Scott County, Indiana HIV outbreak and the high rates of poverty, overdose deaths, and hepatitis B and C. Although HIV has not yet been a significant problem, microepidemics are likely among insular injection drug use (IDU) networks in remote rural areas that remain unidentified due to a weak HIV testing system. Geographic isolation and scarce healthcare resources in WV are also significant challenges to early identification of HIV and prevention of transmission. The long-term objective of this multidisciplinary study team and our established partners statewide is to end the opioid epidemic in WV and its associated consequences of infectious diseases. The overall hypothesis of this study is that, by developing a novel, integrated prevention, harm reduction, and treatment strategy to rapidly identify and mitigate HIV microepidemics, we can limit further spread and reduce hazardous IDU in southern WV. Aim 1. Create an evidence-based road map, working with local communities and public health agencies, to coordinate and improve screening, prevention and treatment for HIV and other IDU-associated diseases. A mixed-methods approach will identify strengths and weaknesses of current testing and public health infrastructure. Aim 2. Develop and test a novel strategy to rapidly identify the emergence of HIV in isolated rural communities. A multicomponent rapid notification ?Opioid Data Repository? will be developed to identify HIV and ?sentinel opioid-related conditions? that can indicate those at risk, IDU prevalence, and the emergence of new HIV (and HCV) cases. Aim 3. Overcome service gaps by deploying an integrated service delivery model based on earlier findings, including evidence-based maps of services and IDU prevalence. Prevention efforts will include enhanced delivery of evidence-based services, implementing novel screening strategies, and integrating existing and enhanced data sources. Improved treatment will result from providing mobile and telehealth services to bridge treatment gaps in isolated areas, and from integrating screening, medical care and addiction treatment. Aim 4. Evaluate the effectiveness (including cost effectiveness), replicability and sustainability of the integrated service delivery model. Making program adjustments based on evaluation and community input is critically important if we are to prevent the devastating effects of an HIV epidemic in these hard-hit communities.